Advances in Life Sciences, particularly in genomics and proteomics, have greatly increased the potential number of reactions and analyses that must be performed by the biotechnology and pharmaceutical industries. An estimated 30 million tests are required to screen a typical pharmaceutical company's compound library against target receptors. The typical number of tests will increase dramatically as information is gleaned from the sequencing of the human genome. To meet these increasing throughput demands in an economically feasible manner, miniaturization of tests is imperative.
Technological advances are enabling the demonstration and use of microscale chemical/biochemical reactions for performing various types of analyses.
Implementation of these reactions at such smaller scales offer economies that are unmatched by conventional approaches. Reduced volumes can lower costs by an order of magnitude but conventional liquid-handling devices fail at the required volumes. Parallel implementation provides even greater advantages as demonstrated by the use of high-density plates for screening and high-density MALDI-TOF plates for mass spectrometry analyses of proteins. The rate-limiting hardware is low volume liquid transfer technology that is robust and scalable for compounds of interest. With growing demand, the development of fluid handling devices adept at manipulating sub-microliter volumes of multiple reagents is needed.
Current systems for handling liquid reagents often employ a “pick and place” technique where a sample from a source plate, usually a microtiter plate, is picked up and placed into another reservoir known as the target plate. This technique is often applied for replicating plates, where scale reduction between the source and the target plates are beneficially realized. Typically, an appropriate volume is aspirated from a source plate and deposited to a target site on a multiple target plate. In this arrangement, reduced sample volumes and sample spacing are required for higher degrees of miniaturization.
In other advancements using “pick and place” distribution, drop-on demand ink jet technology has been adopted for accurately delivering volumes on the order of picoliters. This technology is not only capable of volumetric precision, but also positional accuracy as well. These ink-jet systems typically employ thermal, piezoelectric, or solenoid actuation to deliver defined volumes of liquid sample to precise locations, increasing test site array density.
Two of these approaches, in particular, thermal and piezoelectric ink jet technology, utilize micromachined actuation mechanisms and dispensing orifices which offer non-contact dispensing from the tip without requiring capillary contact for flow purposes. Problematic to these devices is plugging of orifices and scalability. While this printing technology is capable of low-volume, accurate delivery, the initial systems for dispensing chemical reagents lack speed and efficiency due to conventional switching technology. A syringe drive per channel is generally employed, limiting systems to a scale that fails to provide the required throughput. The current systems are unable to quickly switch multiple channels between large-scale metering tasks and subsequent micro dispensing tasks, failing to exploit the advantages and the high speed afforded by this non-contact printing technology.